To develop an animal model of acute lung failure complicating severe septicemia, dose-dependent effects of continuous infusion of Pseudomonas aeruginosa into pigs were determined for infusion rates of 3.10 to the 6th power, 3.10 to the 8th power, and 1.10 to the 9th power bacteria/minute per 20 kg. The higher infusion rates caused severe hypoxemia (mean PaO2 from baseline 78 plus or minus SE 2 to 49 plus 4 or minus 4 mmhg) and increased intrapulmonary shunting following 2-3-fold increases in mean pulmonary artery pressure and resistance. Lung histologic changes included atelectasis, intravascular congestion, and edema. Using this model, we plan to study the ameliorating effects on the pulmonary pathophysiology by: 1) pharmacologic blocking of the mediators of pulmonary hypertension by prostaglandin and histamine inhibition 2) administration of high-dose steroids. In addition, we plan to test the hypothesis that severe hemorrhagic shock preceding the bacterial insult worsens the lung pathophysiology.